The arginine-vasopressin (AVP) is a peptide composed of nine amino acids that is biosynthesized mainly in the hypothalamus and closely involved as a posterior pituitary hormone in the regulation of plasma osmolality, blood pressure, and body fluid volume.
The AVP receptors have so far been cloned in three subtypes, V1a, V1b, and V2 receptors, all of which are known to be seven-transmembrane receptors. The V2 receptor is coupled to Gs to increase the cAMP level. The Via receptor is coupled to Gq/11 to facilitate PI response and increase the intracellular Ca level. The V1a receptor is expressed in the brain, liver, adrenal gland, and vascular smooth muscle, for example, and is involved in the vasoconstrictive action. As is the V1a receptor, the V1b receptor is also coupled to Gq/11 to facilitate PI response (see Non-Patent Documents 1 and 2). The V1b receptor is found most commonly in the pituitary gland (expressed in 90% or more of ACTH secreting cells of the anterior lobe) and is estimated to participate in the AVP-mediated secretion of ACTH from the anterior pituitary. Other than in the pituitary gland, the V1b receptor is widely distributed in the brain and occurs in large amounts not only in the limbic cortex system including the hippocampus, amygdala and entorhinal cortex but also in the cerebral cortex, the olfactory bulb, and the raphe nuclei which are the nuclei of origin of the serotonin nervous system (see Non-Patent Documents 3 and 4).
In recent years, involvement of the V1b receptor in mood disorder or anxiety disorder has been suggested, and usefulness of V1b receptor antagonists is being studied. The V1b receptor KO mice exhibit reduced aggressive behavior (see Non-Patent Document 5). In addition, injection of a V1b receptor antagonist into the septal area prolonged the time spent in the open arms (anxiolytic-like action) in an elevated plus-maze test (see Non-Patent Document 6). In recent years, a peripherally administrable 1,3-dihydro-2H-indol-2-one compound has been created as a V1b receptor specific antagonist (see Patent Documents 1 to 3). Furthermore, the 1,3-dihydro-2H-indol-2-one compound has been reported to show antidepressant and anxiolytic actions in a variety of animal models (see Non-Patent Documents 7 and 8). The compound disclosed in Patent Document 1 has high affinity for the V1b receptor (1×10−9 mol/L to 4×10−9 mol/L) on which it selectively acts; this compound, however, antagonizes AVP, AVP+CRF, and restraint stress-induced ACTH increases.
Recently, V1b receptor antagonists having different structures from the 1,3-dihydro-2H-indol-2-one compound have been reported and they are quinazolin-4-one derivatives (see Patent Documents 4 and 10), β-lactam derivatives (see Patent Documents 5 and 7), azinon/diazinon derivatives (see Patent Document 6), benzimidazolone derivatives (Patent Document 8), isoquinolinone derivatives (see Patent Documents 9 and 10), pyridopyrimidin-4-one derivatives (see Patent Document 11), pyrrolo[1,2-a]pyrazine derivatives (see Patent Document 12), pyrazolo[1,2-a]pyrazine derivatives (see Patent document 13), quinoline derivatives (see Patent Document 14), tetrahydroquinoline sulfonamide derivatives (see Non-Patent Document 9), thiazole derivatives (see Non-Patent Document 10), and sulfonamide derivatives (see Non-Patent Document 11). However, no report has been made of the compounds disclosed in the present invention that have an azole skeleton.